Chlamydiaceae is a family of obligate intracellular parasites. All members share a common developmental cycle. Chlamydia infect a wide range of vertebrate host, particularly humans. Chlamydia trachomitis is one of the two recognized species of Chlamydia. Human infections caused by C. trachomitis. are widespread. This species is one of the most common cause of sexually transmitted disease in the world. It is also one of the main causes of infertility in humans.
The frequency of Chlamydia trachomatis infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Chlamydia trachomatis strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism.
Bacterial protein syntheses is initiated with an N-terminal formyl-methionine. The formate group and methionine are subsequently removed from most proteins in a two step process. Polypeptide deformylase catalyses the first step in this process, removal of the N-terminal formyl group. In E. coli this activity is essential for growth (Mazel, D., Pochet, S., and Marliere, P. (b1994). EMBO J. 13, 914-923). For a review of bacterial polypeptide deformylases see: Mazel, D., Coic, E., Blanchard, S., Saurin, W., and Marliere, P. (1997) J. Mol. Biol. 266, 939-949. The Def from Chlamydia trachomatis described herein is most similar to the peptide deformylase enzyme from Thermus aquaticus (subsp. thermophilus, Swiss Protein entry DEF_THETH, Meinnel T. and Blanquet, S. (1994) J Bacteriol 176: 7387-7390).
Clearly, there is a need for factors, such as the novel compounds of the invention, that have a present benefit of being useful to screen compounds for antibiotic activity. Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease. There is also a need for identification and characterization of such factors and their antagonists and agonists which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptides of the invention have amino acid sequence homology to a known def (thermus thermophilus) protein.